June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
How do outer retinal cells contribute to subretinal drusenoid deposit (SDD) in age-related macular degeneration (AMD)? an ultrastructural and immunohistochemistry investigation
Author Affiliations & Notes
  • Dongfeng Cao
    Ophthalmology and Vision Sciences, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Bibek Adhikari
    Ophthalmology and Vision Sciences, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Jeffrey D. Messinger
    Ophthalmology and Vision Sciences, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Christine A. Curcio
    Ophthalmology and Vision Sciences, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Footnotes
    Commercial Relationships   Dongfeng Cao None; Bibek Adhikari None; Jeffrey Messinger None; Christine Curcio Apellis, Astellas, and Boehringer Ingelheim, Code C (Consultant/Contractor), Genentech/Hoffman LaRoche, Heidelberg Engineering, and Regeneron (outside this project), Code F (Financial Support)
  • Footnotes
    Support  NIH Grant R01EY027948 (Dr. Christine A. Curcio); EyeSight Foundation of Alabama (Birmingham, AL, USA) (CAC); International Retinal Research Foundation (Birmingham, AL, USA) (CAC)
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2124. doi:
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    • Get Citation

      Dongfeng Cao, Bibek Adhikari, Jeffrey D. Messinger, Christine A. Curcio; How do outer retinal cells contribute to subretinal drusenoid deposit (SDD) in age-related macular degeneration (AMD)? an ultrastructural and immunohistochemistry investigation. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2124.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : SDD and soft drusen are risk factors for AMD progression attributed to dysregulated outer retinal lipid transfer. Some outer segment (OS) fragments and opsin immunoreactivity have been reported in SDD (PMID 31599795, 27039021). To determine an ultrastructural basis of photoreceptor-derived material in SDD, deposits were examined by transmission electron microscopy (TEM) and light-microscopy of epitope-specific antibodies for red and green cone opsins (hOPSR-hOPSG).

Methods : Three archival specimens were viewed by TEM: 76-year-old female (PMID 18326750); 88-year-old-male (PMID 35192790); a clinically documented case (Sarks Archive, Sydney Australia). For immunohistochemistry (IHC) donor eyes were screened with ex vivo optical coherence tomography, preserved in 4% paraformaldehyde, and cryosectioned. A red-substrate enzymatic detection system was applied to antibodies to hOPSR-hOPSG (polyclonal #AB5405; monoclonal to N-terminus #MABN249250UG following removal of an N-terminal O-glycosylation motif), and cone arrestin (polyclonal #PA5-84584).

Results : TEM: Examined SDD were at stage 1 (PMID 19815280). Apical processes of the retinal pigment epithelium formed a mat under the smallest deposits and were replaced in larger deposits with apical prolongations of cell body cytoplasm. These lacked melanosomes and maintained contact with OS. Both OS and apical processes formed a sharp border with the extracellular deposit. SDD contained whorls with electron-dense exteriors consistent with lipid and contrasting with smaller lipoprotein-like particles in soft drusen. IHC: With the polyclonal antibody a particulate immunoreactivity was detected through individual SDD, as well as in an apical cap previously shown to have structure of OS disks. No label within SDD was detected using the monoclonal antibody after glycosylase treatment, although surrounding OS had strong signal. SDD labeling with anti-cone arrestin, a cytoplasmic protein, was light and diffuse.

Conclusions : SDD contain lipids and proteins derived from cone OS membranes, in highly modified forms. A sharp boundary between OS and deposits suggests that modification may occur extracellularly. OS contact apical processes well into the SDD growth cycle.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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